Response systems
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2010 senior Scholar Award in aging
The nematode C. elegans has proven to be an invaluable model organism for identifying mechanisms that influence longevity, and may be conserved across species. Recently considerable interest has been focused on how aging is influenced by the target of rapamycin (TOR) signaling pathway. TOR... >> MORE |
2010 senior Scholar Award in aging
We have developed two new model systems that lead to significant increases in mouse maximal longevity. One uses a "Crowded Litter" (CL) approach to reduce food availability, but only in the first 3 weeks of life. The other involves genetic ablation of the gene for MIF, a pro-inflammatory cytokine... >> MORE |
2010 senior Scholar Award in aging
With the support of this award we will apply two "Next Generation" approaches to the study of genetic mouse models in which specific steps of TORC1 signaling (i.e., via the mTOR/raptor complex itself or the downstream proteins 4EBP1 and S6K1) are selectively altered in key young and... >> MORE |
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2009 senior Scholar Award in aging
Mitochondria are cellular organelles that use the oxygen we breathe to oxidize carbohydrates, fats and proteins. The oxygen is fully reduced to form water, and energy is released. The mitochondria capture this energy to phosphorylate ADP to ATP, a molecule that can be hydrolyzed by the cells to... >> MORE |
2009 senior Scholar Award in aging
The long-term objective of our laboratory is to understand the beneficial relationship between hormones and the aging process. Of particular interest is the pituitary hormone, growth hormone, and itís role in metabolism and stress resistance in aging. Our lab has helped to establish a compelling... >> MORE |
2009 senior Scholar Award in aging
We will employ bdelloid rotifers, a group of small, entirely female freshwater invertebrates, as a new, particularly advantageous model system for investigating the processes responsible for aging -- the increase of mortality with increasing age. Initially, we will employ bdelloid rotifers to test... >> MORE |
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2009 senior Scholar Award in aging
Genome damage caused by reactive oxygen species has long been though to be associated with aging and neurodegeneration. Because of limitations in available experimental methods, previous work focused on determining the overall levels of various kinds of oxidative damage. It is likely, though,... >> MORE |
2009 senior Scholar Award in aging
This proposal is to study the role of RIP1 kinase and its signaling pathway in mediating production of an important pro-inflammatory cytokine, TNFα, and its implication in aging. Increased levels of TNFα during aging are detrimental for longevity by contributing to the pathogenesis of... >> MORE |
2008 senior Scholar Award in aging
Oxidative stress has been implicated in the aging process and in the development of many age-related diseases including cancer. My laboratory has focused on studies of a critical consequence of oxidative stress: oxidative damage to DNA. When DNA is oxidized and not properly repaired, mutations and... >> MORE |
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2008 senior Scholar Award in aging
Every day our body must defend itself against countless foreign substances termed xenobiotics. Many of these substances are harmful and over time repeated exposures can damage the body and accelerate the aging process. Our ability to break down and excrete these foreign substances may be one of... >> MORE |
2008 senior Scholar Award in aging
Aging is no less than war waged between chemistry and biochemistry. Chemical reactions result in widespread spontaneous damage to the biomolecules essential for life. However, biochemical reactions can limit or even reverse this damage. Understanding the ability of organisms to mount... >> MORE |
2008 senior Scholar Award in aging
Our laboratory works with an enzyme called PI3 kinase (PI3K). This enzyme has a long history, having first been discovered in the 1980s due to its role in cancer. We now know that PI3K plays a number of important roles in individual cells and in the physiology of the whole organism. For instance... >> MORE |
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2008 senior Scholar Award in aging
There is a great deal of evidence indicating that microglial cell dysfunction plays a role in a variety of neurodegenerative diseases associated with aging, including Alzheimer's, Multiple Sclerosis, Parkinson's Disease and Stroke. Microglia make up approximately 10% of the cells in the brain. They... >> MORE |
2008 senior Scholar Award in aging
We investigate the molecular basis of insulin-like signaling to understand the pathophysiology of metabolic disease that progresses to diabetes and its related disordersóincluding obesity and infertility; cardiovascular; retinal disease; and the regulation of life-span. Our studies reveal common... >> MORE |
2007 senior Scholar Award in aging
Precursor cells that continuously regenerate are vital for health. In order to cure or postpone age-related functional deterioration and disease, it is necessary to identify which precursor cells regulate the rates of aging in various biological systems. Dr. Harrison and his associates are... >> MORE |
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2007 senior Scholar Award in aging
While many factors contribute to longevity, studies over the last decade have revealed particularly important roles for the activity of the insulin and IGF-1 signaling systems. Indeed, these signaling systems have been shown to play a role in control of lifespan in organisms as diverse as worms,... >> MORE |
2007 senior Scholar Award in aging
Substantial epidemiological evidence indicates that conditions in utero program the susceptibility to age-related diseases, in particular atherosclerosis, the underlying cause of most heart attacks and strokes. However, little is known about maternal factors responsible for such... >> MORE |
2006 senior Scholar Award in aging
Decreased insulin-like growth factor (IGF)-I signaling is associated with extended lifespan. However, the underlying mechanisms relating the IGF system and longevity are poorly understood. The IGF system is complex with ubiquitous IGF receptors present on cells to transduce a response, but also... >> MORE |
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2006 senior Scholar Award in aging
The discovery of genes that positively or negatively affect how long an organism lives has been a tremendous advance in the science of aging. While numerous genes have been isolated that affect the longevity of organisms like worms and flies, to date, there have been relatively few genes that... >> MORE |
2006 senior Scholar Award in aging
A consequence of normal cellular respiration is the formation of reactive oxygen species, small molecules that can react with a variety of cellular components. Many studies have suggested that the interaction of reactive oxygen species with cellular structures contributes to aging and... >> MORE |
2005 senior Scholar Award in aging
We are interested in identifying drugs that can delay human aging and extend human lifespan. Such drugs might have beneficial uses, and the analysis of how such drugs work could provide important insights into the regulation of aging. As a first step, we tested whether drugs that are approved... >> MORE |
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2005 senior Scholar Award in aging
My laboratory has been focused on elucidating the function of the Klotho gene. The Klotho gene was originally identified as a gene mutated in a mouse strain that exhibits a syndrome resembling human aging, including a shortened lifespan, skin atrophy, muscle atrophy, neuronal... >> MORE |
2005 senior Scholar Award in aging
Life-long dietary restriction can delay age-related impairments and extend lifespan. However, life-long dietary restriction itself would not be a practical intervention in humans. Therefore many investigators are studying the mechanism by which dietary restriction produces its beneficial... >> MORE |
2005 senior Scholar Award in aging
For unknown reasons, individuals with the metabolic syndrome frequently have high blood pressure, increased blood lipids, reduced exercise capacity, oxidative stress, increased inflammation, glucose intolerance (diabetes), premature cardiovascular disease (atherosclerosis, heart attack and... >> MORE |
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2005 senior Scholar Award in aging
Overview. Living in an aerobic world, oxidative stress has been implicated in the aging process and in the development of a number of age-related, neurological diseases. An organism, however, has means to detoxify reactive oxygen species, including the enzymes glutathione peroxidase,... >> MORE |
2004 senior Scholar Award in aging
The goal of these studies is to clarify the molecular mechanisms for two prominent features of aged organisms: 1) the accumulation of abnormal proteins in cells, and 2) the marked, debilitating loss of muscle mass (sarcopenia). To understand these phenomena, we shall build upon recent advances... >> MORE |
2004 senior Scholar Award in aging
Epigenetics entails the study of the switching on and off of genes during development, cell proliferation and also by environmental insults. Epigenetic changes can result in the stable inheritance of a given spectrum of gene activities in specific cells. Genome modifications resulting from... >> MORE |
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2004 senior Scholar Award in aging
The work by my laboratory at the California Institute of Technology is about understanding bits and pieces of the following large problem: how and why cells destroy their own proteins? A related problem is to understand the consequences of having protein destruction machines in every cell of... >> MORE |
2003 senior Scholar Award in aging
We are studying effects of genes and hormones on aging. We have shown that mutant mice with inherited deficiency of several pituitary hormones live much longer than their normal siblings. These mutants, the Ames dwarf mice, maintain their health, learning abilities, and memory until late in life... >> MORE |
2003 senior Scholar Award in aging
One of the most widely accepted theories in aging research is the free radical or oxidative stress theory of aging, which states that a steady-state accumulation of oxidative damage in cells and tissues leads to aging. Over the past two decades, it has been shown that oxidative damage to cells... >> MORE |
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2002 senior Scholar Award in aging
A decline in the capacity of living organisms to respond vigorously to external stresses (elevated temperature, damaging radiation, reactive chemical agents, etc.) and to maintain homeostasis is a hallmark of aging and is largely responsible for the age-related increase in mortality.... >> MORE |
2002 senior Scholar Award in aging
During the last decade, remarkable discoveries in the small roundworm C. elegans have shown that aging is regulated hormonally by a regulatory system similar to that of the human insulin and IGF-1 (insulin-like growth factor) endocrine systems. This same endocrine system governs the aging... >> MORE |
2002 senior Scholar Award in aging
Hypothesis: Small molecule pharmacological agents, including synthetic hormones, that enhance stress response will slow aging and age-related functional decline. Much of the remarkable progress in the biology of aging has emerged from the lifespan extension paradigm in simple animal... >> MORE |
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2001 senior Scholar Award in aging
Caloric restriction extends life-span in a wide variety of eukaryotic organisms from yeast to mammals. Cellular responses to nutritional availability are mediated by the cAMP signaling pathway in bacteria, cyanobacteria, and unicellular eukaryotes, and Dr. Guarente and co-workers demonstrated... >> MORE |
2001 senior Scholar Award in aging
Generalized aging at the cellular level is thought to arise from the accumulation of damage to protein and nucleic acids that eventually results in the impairment of normal cellular function or transformation of the cells to a cancerous form of growth. How does this damage occur? One hypothesis... >> MORE |
2001 senior Scholar Award in aging
Estrogen appears to protect the aging brain against cognitive dysfunction, neurodegenerative diseases, and brain injury such as stroke. The menopause is accompanied by a dramatic and permanent decrease in estrogen levels. During the past century, the longevity of women has increased from 50 to... >> MORE |
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2000 senior Scholar Award in aging
The present proposal is aimed at testing the hypothesis that activation of brain specific Uncoupling Proteins (UCPs) could prove chronically neuroprotective by providing a combination of two protective measures a) reducing free radical formation, b) reducing the vulnerability of mitochondria to... >> MORE |
2000 senior Scholar Award in aging
Proteins make up a substantial portion of the cell's mass and are involved in most regulated aspects of its activity. They consist of complex polymers of amino acids joined together through peptide bonds. To function, proteins must undergo a folding process that gives them the proper three... >> MORE |
1999 senior Scholar Award in aging
Evidence that oxidative damage, a by-product of normal metabolism in virtually all animals, is causally involved in the process of aging and the development of degenerative disease has been steadily accumulating for more than forty years. An understanding of the exact nature of this damage to... >> MORE |
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1999 senior Scholar Award in aging
Few mammalian models of aging have the phenotype of increased life span. Virtually all work has focused on food restricted (FR) rodents. Although many changes in physiologic function and gene expression have been identified, it is difficult to determine which changes contribute... >> MORE |
1999 senior Scholar Award in aging
We propose to study the importance of a cellular signaling pathway, termed the P13K/Akt/Daf16 pathway, for determining the life span of cells and multi-cellular organisms. Disruption of the P13K/Akt pathway has previously been shown to affect the life span of the invertebrate organism C. ... >> MORE |
2010 new Scholar Award in aging
Aging/longevity is one of the most complex human traits, and is influenced by variations in inherited factors. I will analyze genetic differences of two outbred lines of rat that have been selectively bred for low and high endurance running ability across >26 generations. The low capacity runners... >> MORE |
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2009 new Scholar Award in aging
In humans, aging is associated with two major life-threatening diseases: neurodegeneration and cancer. A number of theories have been proposed to account for the aging process. The stress theory of aging emphasizes that stressful environments cause cellular damages, disruption of cellular functions... >> MORE |
2009 new Scholar Award in aging
Cellular vitality depends upon the cellís ability to produce functional proteins that carry out important activities essential for life. The duration of a cellís life relies in great part on the cellís ability to maintain its critical cohort of proteins in their functional state. The key pathways... >> MORE |
2009 new Scholar Award in aging
My lab is focused on investigating how an animal cell responds to developmental and environmental signals and how this response is manifested in changes in gene expression. The developmental, metabolic, and environmental signals a cell receives induce changes in both RNA and protein synthesis.... >> MORE |
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2009 new Scholar Award in aging
Aging is a complex biological process characterized by progressive functional and structural deterioration of multiple organ systems that eventually cause death. Aging is also an important factor for most of the common diseases, including type 2 diabetes, cardiovascular disease, cancer and... >> MORE |
2009 new Scholar Award in aging
Previous studies have observed greater variation in gene expression in cells from older animals. This suggests that stochasticity in expression could be a cause of aging. We hypothesize that random, stochastic fluctuations in global gene expression can contribute to aging. To test our hypothesis,... >> MORE |
2008 new Scholar Award in aging
Alzheimer's, Parkinson's, and Huntington's diseases are caused by mutant forms of proteins prone to clumping, or aggregation. These diseases are strongly age-associated, suggesting that protein aggregates or the inability to resolve them may worsen with age. Even in cells that do not carry... >> MORE |
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2008 new Scholar Award in aging
The identification of specific genes that regulate the lifespan of different organisms has revealed key determinants of aging beyond environmental stress. While these remarkable discoveries have provided a genetic basis for lifespan, the fundamental mechanisms by which particular genes regulate... >> MORE |
2008 new Scholar Award in aging
Aging is hormonally regulated and we are interested in identifying genetic determinants that function upstream of these endocrine pathways. Recent studies in the nematode Caenorhabditis elegans suggest that altered regulation of steroid and insulin/IGF-1-like hormones can substantially... >> MORE |
2008 new Scholar Award in aging
The free radical theory of aging was proposed by Denham Harman more than 50 years ago, and has been perhaps the most actively studied mechanistic theory of aging. It is based on the idea that oxygen free radicals, in particular mitochondrial superoxide, are normally generated within cells, yet are... >> MORE |
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2008 new Scholar Award in aging
Aging is characterized by the declining ability to respond to stress, increasing homeostatic imbalance, and increased risk of disease. Advanced glycation end-products (AGEs) may provide the scientific explanation for how and why many of the medical complications of the aging process occur. AGEs... >> MORE |
2007 new Scholar Award in aging
Cellular senescence is a state in which cells permanently stop dividing. It occurs in response to cellular stresses, including DNA damage, and also due to shortening of chromosome ends (telomeres) caused by multiple rounds of cell division. Although senescence is believed to protect organisms... >> MORE |
2007 new Scholar Award in aging
In Parkinson's disease the death of dopaminergic neurons in the brain results in the progressive loss of control of body movement. An estimated 1% of the population aged 65 and older suffers from Parkinson's disease, making it the most common neurodegenerative movement disorder. With this... >> MORE |
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2007 new Scholar Award in aging
A major problem during chronological aging is the accumulation of oxidative damage to cellular macromolecules produced by mitochondria-generated reactive oxygen species (ROS). Young cells are protected by a balanced activity of the mitochondria, efficient antioxidant and DNA repair systems, as... >> MORE |
2006 new Scholar Award in aging
The mitochondrial respiratory chain has multiple components (complexes I-V and coenzyme Q) that work intimately together to turn fuel (supplied by the metabolic breakdown of sugar, fat, and protein) into energy (in the form of ATP). It is also a site of production of free radicals, which are... >> MORE |
2006 new Scholar Award in aging
Aging is associated with diminished cognitive function that can, in part, be explained by cellular changes in the mechanisms of neuronal plasticity. Degeneration in synaptic functions associated with learning and memory contributes to age-dependent pathologies including Alzheimer's disease,... >> MORE |
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2005 new Scholar Award in aging
Aging and stress response are both among the most universal of biological processes. Heat-shock Transcription Factor (HSF) is the master regulator of the heat-shock response, a fundamental cellular defensive mechanism against the deleterious effects of various stresses by rapidly expressing a... >> MORE |
2005 new Scholar Award in aging
Misfolded transmembrane and secretory proteins are a feature of several age-associated diseases. The translocation of proteins into the endoplasmic reticulum (ER) and folding are mediated by the translocon and ER chaperones. Oxidative damage of some chaperones in aged tissues suggests folding... >> MORE |
2004 new Scholar Award in aging
The decline in energy with age highlights energy metabolism and the role of mitochondria in aging. Aged cells accumulate oxidative DNA damage that is likely to be responsible for the observed increase in mutations, particularly in the mitochondrial genome. The major source of reactive oxygen... >> MORE |
The Ellison Medical Foundation